We seek support for a Rare Lung Diseases clinical research Consortium (RLDC) facilitating clinical research, training, and education for a group of rare lung diseases based on molecular pathway-driven development of novel diagnostics and therapeutics. The proposed Specific Aims include 1) establish a Consortium focused to Lymphangioleiomyomatosis (LAM), Pulmonary Alveolar Proteinosis (PAP), and Hermansky-Pudlak Syndrome (HPS), 2) conduct longitudinal and therapeutic clinical studies related to LAM, PAP, and HPS at abroad network of rare lung disease clinical centers established initially via LAM clinics, 3) conduct of a Pilot and Demonstration program for the development and evaluation of novel diagnostics, therapeutics, and outcome measures for these and additional 'on-deck' rare lung diseases, 4) provide clinical research training at RLDC clinical centers and attract new investigators to the field, and 5) develop rare lung disease educational materials for patients, medical providers, and the public. Synergies between diseases include the use of quantitative radiological outcome assessment, an emphasis on development and evaluation of blood-based biomarkers and diagnostic tests, and the evaluation of the natural history of each disease. We build on prior successes including development of novel diagnostics (in PAP and LAM), the first successful therapeutic trial for LAM conducted through the RLDC ('MILES'), longstanding partnerships with patient advocacy groups, and a track record of training and career development in rare lung diseases (including a former trainee who is now a project leader in this application). The network consists of three translational sites at Cincinnati Children's (the coordinating center), the University of Cincinnati in Cincinnati, Ohio (a co-directorship), and Vanderbilt, and clinical research sites selected from the existing LAM Clinic Network. Participating patient support groups include the LAM Foundation, PAP Foundation, HPS Network, and the Alpha-1 Foundation. These centers and Foundations are already closely integrated with clinical sites chosen from active networks of collaborating clinical centers that include over 28 sites in 22 states distributed throughout the United States. Participating translational centers will leverage resources from existing NIH Clinical and Translational Science Awards (CTSA) and a racially diverse population that includes pediatric opportunities. Each center provides ongoing longitudinal clinical studies, an excellent clinical training program, and active clinical programs designed to test novel therapies, develop diagnostic tests and evaluate outcome measures that will lead to new therapies and improve the lives of affected